rs1805018

chr6-46711566-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005084.4(PLA2G7):c.593T>C(p.Ile198Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0628 in 1,613,464 control chromosomes in the GnomAD database, including 4,853 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (1216 hom., cov: 32)
  • Exomes 𝑓: 0.059 (3637 hom.)
• Consequence: PLA2G7 NM_005084.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -1.09

Genes affected

PLA2G7 (HGNC:9040): (phospholipase A2 group VII) The protein encoded by this gene is a secreted enzyme that catalyzes the degradation of platelet-activating factor to biologically inactive products. Defects in this gene are a cause of platelet-activating factor acetylhydrolase deficiency. Two transcript variants encoding the same protein have been found for this gene.[provided by RefSeq, Dec 2009]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018128157).
• BP6: Variant 6-46711566-A-G is Benign according to our data. Variant chr6-46711566-A-G is described in ClinVar as [Benign]. Clinvar id is 7915.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLA2G7	NM_005084.4	c.593T>C	p.Ile198Thr	missense_variant	7/12	ENST00000274793.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLA2G7	ENST00000274793.12	c.593T>C	p.Ile198Thr	missense_variant	7/12	1	NM_005084.4	P1
PLA2G7	ENST00000537365.1	c.593T>C	p.Ile198Thr	missense_variant	7/12	1		P1

Frequencies

GnomAD3 genomes AF: 0.0994 AC: 15116 AN: 152020 Hom.: 1210 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0570

Gnomad ASJ AF: 0.0706

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0312

Gnomad MID AF: 0.0892

Gnomad NFE AF: 0.0472

Gnomad OTH AF: 0.0894

GnomAD3 exomes AF: 0.0680 AC: 17097 AN: 251296 Hom.: 873 AF XY: 0.0680 AC XY: 9233 AN XY: 135806

Gnomad AFR exome AF: 0.223

Gnomad AMR exome AF: 0.0379

Gnomad ASJ exome AF: 0.0701

Gnomad EAS exome AF: 0.0960

Gnomad SAS exome AF: 0.109

Gnomad FIN exome AF: 0.0297

Gnomad NFE exome AF: 0.0468

Gnomad OTH exome AF: 0.0653

GnomAD4 exome AF: 0.0590 AC: 86253 AN: 1461326 Hom.: 3637 Cov.: 31 AF XY: 0.0600 AC XY: 43614 AN XY: 727000

Gnomad4 AFR exome AF: 0.226

Gnomad4 AMR exome AF: 0.0402

Gnomad4 ASJ exome AF: 0.0680

Gnomad4 EAS exome AF: 0.161

Gnomad4 SAS exome AF: 0.108

Gnomad4 FIN exome AF: 0.0325

Gnomad4 NFE exome AF: 0.0476

Gnomad4 OTH exome AF: 0.0698

GnomAD4 genome AF: 0.0995 AC: 15138 AN: 152138 Hom.: 1216 Cov.: 32 AF XY: 0.0994 AC XY: 7392 AN XY: 74378

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.0569

Gnomad4 ASJ AF: 0.0706

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.0312

Gnomad4 NFE AF: 0.0472

Gnomad4 OTH AF: 0.0903

Alfa AF: 0.0598 Hom.: 984

Bravo AF: 0.104

TwinsUK AF: 0.0429 AC: 159

ALSPAC AF: 0.0418 AC: 161

ESP6500AA AF: 0.213 AC: 940

ESP6500EA AF: 0.0509 AC: 438

ExAC AF: 0.0731 AC: 8871

Asia WGS AF: 0.135 AC: 470 AN: 3478

EpiCase AF: 0.0515

EpiControl AF: 0.0512

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

RECLASSIFIED - POLYMORPHISM Benign:1

Benign, no assertion criteria provided

literature only

OMIM

May 01, 2000

- -

PLA2G7-related condition Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 23, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.69
Cadd	Benign	0.017
Dann	Benign	0.35
DEOGEN2	Benign	0.041	T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0014	N
MetaRNN	Benign	0.0018	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.14	N;N
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	1.2	N;N
REVEL	Benign	0.016
Sift	Benign	0.65	T;T
Sift4G	Benign	0.58	T;T
Polyphen		0.0	B;B
Vest4		0.031
MPC		0.0044
ClinPred		0.0028	T
GERP RS		-7.6
Varity_R		0.15
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1805018; hg19: chr6-46679303; COSMIC: COSV51261912;